摘要
目的 探讨RAS基因相关性自身免疫淋巴增殖性疾病（RALD）的临床特征及基因变异特点.方法 回顾性分析2012年1月至2017年1月深圳市儿童医院风湿免疫科住院诊治的2例RALD的临床资料及基因变异特点,以基因NRAS、KRAS或RALD为检索词,检索PubMed、中国知网、重庆维普及万方数据库2000年1月—2017年1月RAS基因变异相关文献.总结RALD的临床特征及基因变异特点.结果 例1女,7岁7月龄,发现血小板减少、脾大3年余,下肢可见陈旧性瘀斑,颌下淋巴结肿大,肝脏右肋下8 cm,脾脏脐下1 cm;血小板波动于（15~60）×109/L,血红蛋白57 g/L,抗人球蛋白试验阳性;胸部CT示双肺间质性病变、双侧胸腔积液、心包积液、心肌内膜及心肌损害、腹腔积液.例2女,7岁5月龄,反复血小板减少7余年,间断眼睑、腹部肿胀3年,颈部及右侧腹股沟淋巴结肿大,肝脏肋下平脐,剑突下6 cm,脾脏肋下5 cm;血小板9×109/L,单核细胞5.46×109/L,骨髓涂片显示原始幼稚细胞比例增高（0.09~0.11）,胸部CT示肺炎伴间质性病变、中大量心包积液、心脏增大、肺动脉高压.基因检测：例1存在KRAS基因2号外显子c.35G〉A、p.G12D体细胞突变,例2存在NRAS基因2号外显子c.38G〉A、p.G13D体细胞突变.共检索到相关英文文献7篇,中文文献1篇.其中NRAS基因发生体细胞突变所致RALD患者10例,KRAS基因发生体细胞突变所致RALD患者13例,23例患者主要临床特征包括高γ球蛋白血症、脾脏肿大、单核细胞或B细胞增生症.结论 RALD常以肝脾肿大、淋巴组织增生、自身免疫性血细胞减少、B细胞或单核细胞增多症、高球蛋白血症起病,明确RAS基因体细胞突变分析有助于诊断此病.
Objective To investigate the clinical features and genetic characteristics of cases with Ras-associated autoimmune leukoproliferative disorder（RALD）. Method Characteristics of clinical data and gene mutation of the first two cases in China with RALD were retrospectively analyzed. The related literature was searched by using search terms＂NRAS＂,＂KRAS＂or＂RALD＂. Result Case1, a seven-year-seven-month old girl, was admitted due to＂thrombocytopenia and splenomegaly for three years＂. Palpation showed enlargement of submandibular lymph nodes and hepatosplenomegaly.The platelet count fluctuated between 15 × 109/L and 60 × 109/L. Hemoglobin was as 57 g/L and Coomb＇＇s test was positive.Lung computed tomography revealed interstitial lung disease, bilateral pleural effusion, pericardial effusion, myocardial injury and ascites. Case2, a seven-year-five-month old girl, was admitted due to＂recurrent thrombocytopenia for seven years , intermittent eyelid and abdominal swelling for three years＂. Palpation showed enlargement of cervical and right inguinal lymph nodes, and hepatosplenomegaly.The number of platelet and monocyte were 9×109/L and 5.46×109/L, respectively. Bone marrow smear revealed an increase in the proportion of primitive immature cells （0.09 to 0.11）. Lung computed tomography revealed interstitial lung disease, pericardial effusion, cardiac enlargement and pulmonary hypertension. The gene sequencing＆nbsp;results showed KRAS gene c.38G〉A somatic mutation in case1, and p.G12D and NRAS gene c.38G〉A, p. G13D somatic mutation in case2. A total of 8 reports were retrieved including 23 cases caused by NRAS（10 cases） or KRAS（13 cases） gene somatic mutation. All the 23 cases showed hypergammaglobulinemia, splenomegaly, B cells hyperplasia or mononucleosis. Conclusion RALD often manifests as hepatosplenomegaly,lymphoproliferation, autoimmune hematocytopenia, B cells hyperplasia or mononucleosis, hypergammaglobulinemia. Gene sequencing analysis can help diagnose the disease.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2017年第11期853-857,共5页
Chinese Journal of Pediatrics
